Title 40

SECTION 799.3300

799.3300 Unsubstituted phenylenediamines.

§ 799.3300 Unsubstituted phenylenediamines.

(a) Identification of test substance. (1) The unsubstituted phenylenediamines (pda's), para-phenylenediamine (p-pda, CAS No. 106-50-3), or its sulfate salt (p-pda.H2SO4, CAS No. 1624-57-75), meta-phenylenediamine (m-pda, CAS No. 108-45-2), or its sulfate salt (m-pda.H2SO4, CAS No. 54-17-08), and ortho-phenylenediamine (o-pda, CAS No. 95-54-5) shall be tested in accordance with this section.

(2) p-Pda, m-pda, and o-pda of at least 98 percent purity shall be used as the test substances. Either the hydrochloride or sulfate salt of m-pda shall be used as the test substances. Either the hydrochloride or sulfate salt of m-pda shall be used as a test substance in the oncogenicity test in paragraph (c)(2) of this section if the free base proves to be unstable under the conditions of this study. Either the hydrochloride or sulfate salt of o-pda, p-pda, or m-pda shall be used as a test substance in the 90-day subchronic neurotoxicity studies in paragraph (c)(3)(B) of this section if the free base proves to be unstable under the conditions of these studies. The salt(s) shall be of at least 98 percent purity.

(b) Persons required to submit study plans, conduct tests, and submit data. (1) All persons who manufacture (including import or by-product manufacture) or process m-pda or m-pda.H2SO4, or intend to manufacture or process m-pda or m-pda.H2SO4, after the effective date of this rule to the end of the reimbursement period shall submit letters of intent to test, submit study plans, conduct tests, and submit data, or submit exemption applications as specified in paragraphs (c), (d), and (e) of this section, subpart A of this part, and parts 790 and 792 of this chapter for single-phase rulemaking.

(2) All persons who manufacture (including import or by-product manufacture) or process p-pda, or p-pda.H2SO4, or intend to manufacture or process p-pda, or p-pda H2SO4, after the effective date of this rule to the end of the reimbursement period shall submit letters of intent to test, submit study plans, conduct tests, and submit data, or submit exemption applications as specified in paragraphs (c)(3), (d), and (e) of this section, subpart A of this part and parts 790 and 792 of this chapter for single-phase rulemaking.

(3) All persons who manufacture (including import or by-product manufacture) or process o-pda, or intend to manufacture or process o-pda after the effective date of this rule to the end of the reimbursement period shall submit letters of intent to test, submit study plans, conduct tests, and submit data, or submit exemption applications as specified in paragraphs (c)(3), (d), and (e) of this section, subpart A of this part, and parts 790 and 792 of this chapter for single-phase rulemaking.

(c) Health effects testing - (1) Mutagenicity testing - (i) Required testing. (A) The sex-linked recessive lethal (SLRL) assay shall be conducted, by injection, in Drosophila melanogaster with m-pda in accordance with § 798.5275 of this chapter.

(B) If the SLRL assay conducted pursuant to paragraph (c)(1)(i)(A) of this section is positive, either the mouse visible specific locus test (MVSL) or the mouse biochemical specific locus test (MBSL) shall be conducted for m-pda by gavage in accordance with §§ 798.5200 or 798.5195 of this chapter, if after public program review, EPA issues a Federal Register notice or sends a certified letter to the test sponsor(s) specifying that testing shall be initiated. The test sponsor shall notify EPA of its choice in writing in its first interim report.

(C) The mouse bone marrow cytogenetics: micronucleus (MBMC) assay shall be conducted on m-pda in accordance with § 798.5395 of this chapter.

(D) If the MBMC assay conducted pursuant to paragraph (c)(1)(i)(C) of this section is positive, the dominant lethal assay (DL) in mice shall be conducted on m-pda pursuant to § 798.5450 of this chapter.

(E) If the DL conducted pursuant to paragraph (c)(1)(i)(D) of this section is positive, heritable translocation (HT) testing in the mouse on m-pda shall be conducted pursuant to § 798.5460 of this chapter, if after a public program review, EPA issues a Federal Register notice or sends a certified letter to the test sponsor(s) specifying that testing shall be initiated.

(ii) Reporting requirements. (A) The tests shall be completed and the final reports for the MBMC assay shall be submitted to the EPA no later than January 16, 1991. The final report for the SLRL in Drosophila melanogaster shall be submitted no later than April 15, 1991.

(B) If required, the DL test shall be completed and the final report shall be received by EPA no later than 24 months after the effective date of this final rule.

(C) If required, the MVSL or the MBSL shall be completed and the final report shall be received by EPA no later than 51 months after EPA issues a Federal Register Notice or sends a certified letter to the test sponsor(s) identified under paragraph (c)(1)(i)(B) of this section specifying that testing shall be initiated.

(D) If required, the HT test shall be completed and the final report shall be submitted to EPA not later than 36 months after the date on which EPA notifies the test sponsor under paragraph (c)(1)(i)(E) of this section to begin testing.

(E) Interim reports for the SLRL assay and MBMC are required at 6-month intervals beginning 6 months after the effective date of this section. If the DL is triggered, interim reports are required at 6 month intervals beginning with the date of initiation of the study.

(F) Interim reports for the HT and either the MBSL or MVSL are required at 6-month intervals beginning 6 months after the date of notification by EPA that testing shall be initiated, and ending when the final report is submitted.

(2) Oncogenicity - (i) Required testing. A 2-year dermal oncogenicity bioassay shall be conducted with m-pda if, after public program review, EPA issues a Federal Register notice specifying that the testing shall be initiated.

(ii) [Reserved]

(iii) Reporting requirements. (A) The final results and final report for the oncogenicity bioassay shall be submitted to EPA no later than 53 months after EPA issues a Federal Register notice or sends a certified letter to the test sponsor under paragraph (c)(2)(i) of this section specifying that the testing shall be initiated.

(B) Interim reports for the oncogenicity study are required at 6-month intervals beginning 6 months after the date of notification by EPA that testing shall be initiated and ending when the final report is submitted.

(3) Neurotoxicity - (i) Required testing. (A) Acute neurotoxicity testing in the neurotoxicity functional observational battery (FOB) in accordance with § 798.6050 of this chapter, and the motor activity test (MAT) in accordance with § 798.6200 of this chapter, shall be conducted for o-, m-, and p-pda. The test chemicals shall be administered in a single oral dose. Clinical observations shall be made at a minimum of 1, 4, 24, and 48 hours and at 7 days after dosing.

(B) If neurotoxic effects are observed at 24 hours, or longer, during the testing conducted pursuant to paragraph (c)(3)(i)(A) of this section, then 90-day subchronic neurotoxic FOB and MAT tests shall be conducted in accordance with §§ 798.6050 and 798.6200 of this chapter, respectively, for each isomer showing such effects. At the end of these tests, the animals shall be sacrificed and the nervous tissue preserved and examined as described in the neuropathology test standard, § 798.6400 of this chapter.

(ii) Reporting requirements. (A) The acute neurotoxicity tests shall be completed and the final report submitted to EPA no later than September 15, 1990. If triggered, the final report of the subchronic neurotoxicity testing and the neuropathological examination shall be submitted to EPA on the following schedules. If one isomer is triggered, the reporting deadline is July 15, 1990. If two isomers are triggered, the reporting deadline is January 15, 1992. If three isomers are triggered, the reporting deadline is July 15, 1992.

(B) [Reserved]

(d) Chemical fate testing - (1) Indirect photolysis testing - (i) Required testing. Indirect photolysis studies shall be conducted with p-, m-, and o-pda to determine the half-life in water of each of the three unsubstituted pda's in accordance with § 795.70 of this chapter.

(ii) Reporting requirements. (A) The final report shall be submitted to EPA no later than 8 months after the effective date of the final rule.

(B) The final report shall include a calculation of the predicted environmental concentration (PEC), 100 × PEC, and 1,000 × PEC for each isomer. PEC shall be calculated by using results from the indirect photolysis studies and solving the following equations for the appropriate isomer: o-pda: PECo = 0.3629 + 1.0468 log t 1/2; m-pda: PECm = 0.6830 + 1.9702 log t 1/2; p-pda: PECp = 0.0085 + 0.0024 log t 1/2, where PEC is the predicted concentration in ppb and t 1/2 is the half-life for oxidation (i.e., indirect photolysis) expressed in minutes. PEC, 100 × PEC, and 1,000 × PEC shall be used in the decision logic described in paragraph (e) of this section.

(2) [Reserved]

(e) Environmental effects testing - (1) Acute toxicity testing - (i) Required testing. (A) Flow-through fish acute toxicity tests in the rainbow trout (Salmo gairdneri) shall be conducted with o-, m-, and p-pda in accordance with § 797.1400 of this chapter.

(B) Acute flow-through studies on the freshwater invertebrate Gammarus shall be conducted with o-, m-, and p-pda in accordance with § 795.120 of this chapter.

(C) If the concentration affecting 50 percent of the population (LC50 or EC50) for any study conducted pursuant to paragraphs (e)(1)(i)(A) and (B) of this section is less than or equal to 100 × PEC, less than or equal to 1 milligram/liter (mg/L), or less than or equal to 100 mg/L and shows indications of chronicity, chronic toxicity testing shall be conducted pursuant to paragraph (e)(2) of this section. Indications of chronicity shall be the following: for fish or aquatic invertebrates, the ratio of 24 hour/96 hour LC50s is greater than or equal to 2; for gammarids, the ratio of 24 hour/48 hour EC50s is greater than or equal to 2.

(ii) Reporting requirements. The final reports for acute toxicity testing shall be submitted as follows:

(A) Testing on the rainbow trout shall be completed and submitted to EPA 9 months after the effective date of the final rule for o-pda and p-pda. Testing for m-pda shall be completed and submitted by January 15, 1991.

(B) The acute toxicity testing in freshwater Gammarus shall be completed and submitted no later than January 15, 1991.

(2) Chronic toxicity testing - (i) Required testing. (A) A fish partial life-cycle flow-through test shall be conducted in the more sensitive fish species, either Pimephales promelas or Salmo gairdneri, with each isomer, o-, m-, and p-pda, demonstrating an LC50, determined by testing of fish pursuant to paragraph (e)(1)(i)(A) of this section, equal to or less than 100 × PEC; or less than 1 mg/L; or less than 100 mg/L with indications of chronicity. Chronicity indicators are defined in paragraph (e)(1)(i)(C) of this section. Testing shall be conducted in accordance with § 797.1600 of this chapter.

(B) An invertebrate life-cycle flow-through toxicity test shall be conducted in Daphnia magna for o- and p-pda in accordance with § 797.1330 of this chapter.

(ii) Reporting requirements. (A) The fish partial life-cycle flow-through test shall be completed and final results shall be submitted to EPA no later than December 1, 1992.

(B) The invertebrate life-cycle flow-through toxicity test shall be completed and the final report submitted to EPA no later than January 15, 1993.

(f) Effective dates. (1) The effective date of this final rule is January 16, 1990, except for paragraphs (c)(1)(i)(B), (c)(1)(ii)(A), (c)(1)(ii)(C), (c)(1)(ii)(F), (c)(3)(ii)(A), (e)(1)(ii), (e)(2)(ii)(A), and (e)(2)(ii)(B) of this section. The effective date for paragraphs (c)(1)(i)(B), (c)(1)(ii)(C), and (c)(1)(ii)(F) of this section is May 21, 1990. The effective date for paragraphs (c)(1)(ii)(A), (c)(3)(ii)(A), and (e)(1)(ii), of this section is May 21, 1991. The effective date for paragraph (e)(2)(ii)(A) is June 12, 1992. The effective date for paragraph (e)(2)(ii)(B) is May 28, 1993.

(2) The guidelines and other test methods cited in this rule are referenced as they exist on the effective date of the final rule.

[54 FR 49294, Nov. 30, 1989, as amended at 55 FR 12644, Apr. 5, 1990; 56 FR 23231, May 21, 1991; 57 FR 24961, June 12, 1992; 58 FR 30992, May 28, 1993; 58 FR 34205, June 23, 1993]